Major histocompatibility complex class I expression impacts on patient survival and type and density of immune cells in biliary tract cancer

Abstract

Background:Biliary tract cancers (BTC) are rare malignant tumours with a poor prognosis. Previously, we have presented a detailed characterisation of the inflammatory infiltrate in BTC. Here, we analysed the impact of the expression of major histocompatibility complex class I (MHC I) on patient survival and the quantity, as well as the quality of tumour-infiltrating immune cell types in BTC.Methods:MHC I expression was assessed semi-quantitatively in 334 BTC, including extrahepatic (n=129) and intrahepatic cholangiocarcinomas (n=146), as well as adenocarcinomas of the gallbladder (n=59). In addition, 71 high-grade biliary intraepithelial lesions (BilIN 3) were included. Results were correlated with data on antitumour inflammation and investigated with respect to their association with clinicopathological variables and patient survival.Results:BTC showed a wide spectrum of different MHC I expression patterns ranging from complete negativity in some tumours to strong homogenous expression in others. In BilIN 3, significantly higher MHC I expression levels were seen compared to invasive tumours (P=0.004). Patients with strong tumoural MHC I expression had a significantly higher overall survival probability (median survival benefit: 8 months; P=0.006). MHC I expression strongly correlated with the number of tumour-infiltrating T-lymphocytes (CD4+ and CD8+) and macrophages.Conclusions:Differences of MHC I expression predict patient outcome and show correlations with specific components of the inflammatory infiltrate in BTC. These findings contribute to a better understanding of immune response and immune escape phenomena in cholangiocarcinogenesis.

The tumour microenvironment and immune milieu of cholangiocarcinoma

“…Furthermore, FoxP3 overexpression is accompanied by CTLA‐4 overexpression . Indeed, CTLA‐4 is expressed on the surface of Tregs and has to bind to CD80 on antigen‐presenting cells to exert inhibitory effects on cytotoxic cells . Interestingly, a deregulation of genes related to immune modulation in BTCs was more pronounced in the peritumoural than in the tumour tissue and facilitated tumour recurrence and chemo‐resistance.…”

Activation or suppression of the immune response mediators in biliary tract cancer (BTC) patients: a systematic review and meta-analysis

“…In comparison, intraepithelial tumor-infiltrating CD4+, CD8+, and Foxp3+ T lymphocytes, MHC I and NKG2D were referred as positive factors to prolong the overall survival of patients with BTC. The role of intraepithelial tumor-infiltrating CD8+ T lymphocytes, MHC I and NKG2D has been identified and reported a beneficial prognostic effect of high cell counts in a variety of human malignancies including BTC 8, 9, 11, 12, 27, 30-32. Goepport also found a better prognostic impact of both intraepithelial tumor-infiltrating CD4+ and Foxp3+ T lymphocytes.…”

“…Studies identified immune cell types or ratio including CD4+, CD8+, and Foxp3+ Tumor-infiltrating T lymphocytes (TILs), IL17+, neutrophil recruitment (CD66b+), PD-1/CD8 TILs and neutrophil/lymphocyte (NLR), and analyzed the distribution and clinical relevance of these mediators 8, 10, 12-14. Others observed the impact of the expression of major histocompatibility complex class I (MHC I) and natural killer group 2 member D (NKG2D) 9, 11.…”

Treating Hepatobiliary Cancer: The Immunologic Approach

“…HCCs express low levels of MHC class I molecules in addition to costimulatory molecules [33] . Similarly, in BTC, Goeppert et al [34] analysed the impact of MHC expression on survival in a large series of patients ( n = 334) as well as the relationship of this to TIL. MHC I expression was assessed semi-quantitatively and divided into 2 groups of high and low expression.…”